Phase I/II Trial of SPK-8011: Stable and Durable FVIII Expression for > 2 Years With Significant ABR Improvements in Initial Dose Cohorts Following AAV-Mediated FVIII Gene Transfer for Hemophilia A
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Phase I/II Trial of SPK-8011: Stable and Durable FVIII Expression for > 2 Years With Significant ABR Improvements in Initial Dose Cohorts Following AAV-Mediated FVIII Gene Transfer for Hemophilia A

L. George1,2, E. Eyster3, M. Ragni4, S. Sullivan5, B. Samelson-Jones1,2, M. Evans3, A. MacDougall6, M. Curran6, S. Tompkins6, K. Wachtel6, D. Takefman6, K. Reape6, F. Mingozzi6, P. Monahan6, X. Anguela6, K. High6

1Children's Hospital of Philadelphia, Philadelphia, United States

2Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States

3Pennsylvania State University Milton S. Hershey Medical Center, Hershey, United States

4University of Pittsburgh Medical Center and Hemophilia Center of Western Pennsylvania, Department of Medicine, Pittsburgh, United States

5Mississippi Center for Advanced Medicine, Madison, United States

6Spark Therapeutics, Philadelphia, United States

Key Data Points

The phase 1/2 trial designed for SPK-8011 included patients infused with 1 of 3 vector doses: 5x1011 vg/kg (5e11, n = 2), 1x1012 vg/kg (1e12, n = 3), and 2x1012 vg/kg (2e12, n = 9). Eligible patients were adult males with moderate (n = 1) to severe (n = 13) hemophilia A (FVIII:C ≤ 2%), low to undetectable levels of neutralizing antibodies to capsid LK03, and exposure to factor for > 150 days with no history of inhibitors. Patients were followed closely for 1 year, with long-term follow-up planned for up to 4 years.

Of the 14 patients infused with SPK-8011, 2 patients infused with the highest dose (2e12) did not maintain stable expression of FVIII. The 12 patients with stable expression demonstrated a 91% reduction in bleeding events and a 96% reduction in factor usage (not shown).

Based on the one stage assay, expression of FVIII for patients in the low dose cohort (5e11, participants 1 and 2 in graph) and middle dose cohort (1e12, participants 3-5 in graph) were between 5% and 25% for long-term follow-up durations of 2 to 3.3 years.

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